DESCRIPTION (Taken from the Application): The objective of this proposal is to establish a Structural Genomic Center in Berkeley to focus an integrated structural genomics effort on the genomes of Mycoplasma genitalium and M. pneumoniae. The aims are 1) to obtain the three-dimensional folds for most of the fold families represented in these minimal genomes; 2) to determine the structures for representative proteins from each fold family; and 3) to infer the molecular functions of the proteins with no known functions. The molecular functions inferred from the structures will be correlated with cellular function whenever possible. The resulting information will be a significant step toward understanding the relationship between protein structure and molecular function. Further, this pilot project will serve to develop and test the elements necessary for subsequent structural genomics efforts for other organisms. The investigators will seek to optimize and, to the extent possible, to automate all key processes of a high-throughput structure-determination effort. These processes include target selection, gene cloning and overexpression, protein purification, structure determination, and results dissemination. Significant components of our effort will be devoted to optimization of overexpression vectors; hardware development for crystal screening and assessment, diffraction data collection, and data processing; development of improved methods for structure determination and refinement; and development of data management systems.